Clinical characteristics and cardiometabolic association of non-suppressed cortisol after dexamethasone suppression test in patients with pheochromocytoma

Abstract Objective Catecholamine excess in pheochromocytoma may contribute to elevated serum cortisol concentration. However, the clinical characteristics and cardiometabolic effects of concurrent non-suppressed cortisol concentration remain unclear. Design Retrospective multicenter cohort study. Materials and Methods Among 806 patients with pheochromocytoma from five tertiary centers, 389 who underwent a 1-mg overnight dexamethasone suppression test (ODST) were included. Non-suppressed cortisol was defined as a post-ODST cortisol concentration >1.8 μg/dL. Clinical and tumor characteristics were compared between patients with and without non-suppressed cortisol. Correlations between post-ODST cortisol concentration and catecholamine concentrations were analyzed. Logistic regression analyses identified factors associated with type 2 diabetes mellitus (T2DM) and hypertension (HTN). Results Non-suppressed cortisol was identified in 144 patients (37.0%). Despite comparable body mass index (BMI) (22.9 vs. 23.6 kg/m², P = 0.050), patients with non-suppressed cortisol had more frequent HTN (61.1% vs. 46.1%, P = 0.004) and T2DM (31.3% vs. 17.1%, P = 0.001), larger tumors (4.0 vs. 3.6 cm, P = 0.021), and more frequent bilaterality (9.7% vs. 4.1%, P = 0.026). Post-ODST cortisol concentration was positively correlated with plasma metanephrine (r = 0.148, P = 0.011) and normetanephrine (r = 0.141, P = 0.016). Non-suppressed cortisol was independently associated with T2DM (odds ratio [OR] = 2.072; 95% confidence interval [CI] = 1.137–3.777; P = 0.017) and HTN (OR = 1.905; 95% CI = 1.079–3.361; P = 0.026). Conclusions Larger tumor size, bilaterality, and higher plasma metanephrine and normetanephrine levels were associated with non-suppressed post-ODST cortisol. Post-ODST cortisol >1.8 μg/dL in patients with pheochromocytoma was independently linked to a higher prevalence of T2DM and HTN, suggesting an additive cardiometabolic burden.